Functional Characterization of Multiple Transactivating Elements in β-Catenin, Some of Which Interact with the TATA-binding Proteinin Vitro*
Abstract
β-Catenin, a member of the family of Armadillo repeat proteins, plays a dual role in cadherin-mediated cell adhesion and in signaling by Wnt growth factors. Upon Wnt stimulation β-catenin undergoes nuclear translocation and serves as transcriptional coactivator of T cell factor DNA-binding proteins. Previously the transactivation potential of different portions of β-catenin has been demonstrated, but the precise location of transactivating elements has not been established. Also, the mechanism of transactivation by β-catenin and the molecular basis for functional differences between β-catenin and the closely related proteins Armadillo and Plakoglobin are poorly understood. Here we have used a yeast system for the detailed characterization of the transactivation properties of β-catenin. We show that its transactivation domains possess a modular structure, consist of multiple subelements that cover broad regions at its N and C termini, and extend considerably into the Armadillo repeat region. Compared with β-catenin the N termini of Plakoglobin and Armadillo have different transactivation capacities that may explain their distinct signaling properties. Furthermore, transactivating elements of β-catenin interact specifically and directly with the TATA-binding proteinin vitro providing further evidence that a major function of β-catenin during Wnt signaling is to recruit the basal transcription machinery to promoter regions of Wnt target genes.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed. Tel.: 49-761-5108-477; Fax: 49-761-5108-474; E-mail: hecht{at}immunbio.mpg.de.
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↵§ Present address: Institute of Clinical Chemistry and Pathobiochemistry, Benjamin Franklin University Hospital, Hindenburgdamm 20, D-12200 Berlin, Germany.
- Abbreviations:
- Arm
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Armadillo
- CBD
-
catenin-binding domain
- DBD
-
DNA-binding domain
- GST
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glutathioneS-transferase
- GTF
-
general transcription factor
- LEF-1
-
lymphoid enhancer factor 1
- PAGE
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polyacrylamide gel electrophoresis
- TAD
-
transactivation domain
- TBP
-
TATA-binding protein
- TCF
-
T cell factor
- TLE
-
transducin-like enhancer of split
- WT
-
wild type
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- Received February 4, 1999.
- Revision received March 30, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
